The administrative structure for this program project resides within the UCLA Brain Injury Research Center (BIRC) under the direction of David A. Hovda, Ph.D. The center will provide administrative support for the current application. Consequently, the current application does not request money for administrative staff or consumable expenses. The UCLA BIRC will also support supplies, equipment (and upgrades), travel, and imaging scans. This allows for the majority of funding provided to this program from NIH to be applied directly to research. As Principal Investigator for this application, Dr. Hovda will be responsible for all aspects of the program. Dr. Neil Martin (Chief of the Division of Neurosurgery) will have a specific role in the leadership of this program project. As Chief of the Division and Director of the UCLA Neurosurgery Residency Program, Dr. Martin will be responsible for maintaining the commitment by the clinical staff and Division administration to the research activities outlined within this proposal. It should be noted that the Division of Neurosurgery will become an independent Department July 1, 2008. Dr. Neil Martin has been named Chairman of the new Department of Neurosurgery at the David Geffen School of Medicine at UCLA. Day-to-day operations of the research outlined within this proposal will be evaluated on a weekly basis. The faculty and staff of the UCLA BIRC meet every Wednesday from 10:00 AM - 12:00 Noon in the Stern Conference room located within the Division of Neurosurgery. This conference room contains audio-visual equipment and computer support providing access to both clinical and basic science databases. During these meetings, all investigators participate in discussions related to all aspects of the program including space allocation, new recruitments, budgets, public relations, scientific merit, teaching, upcoming scientific meetings and publications. In addition to these programmatic issues, all investigators evaluate the current status of research subjects and review the process of alerting the clinical research team of any new traumatically brain injured patients. One BIRC meeting every month is dedicated to patient presentation where all the collected data on an individual subject is presented and discussed. Another meeting every month is dedicated to the presentation of science by one of the key investigators in the program. This schedule assures that basic scientists are exposed to the clinical research and management issues related to human TBI. Conversely, having basic scientists present their research on a monthly basis assures that clinical scientists are exposed to the most current scientific issues related to the neurobiology of TBI. Attendance is recorded and minutes are distributed for each meeting. In addition to these general weekly UCLA BIRC meetings, the Principal Investigators of the individual projects and the leaders of the individual cores make up a "Principal Investigators" Committee. This Committee meets as issues arise that are deemed by Dr. Hovda as inappropriate for general discussion by the entire research staff. These topics include performance evaluations, authorship, interpersonal and ethical issues related to scientific integrity. 1.2 The Overall Mission of the UCLA BIRC The primary mission of the UCLA Brain Injury Research Center (BIRC) is to advance the understanding of the neurobiology of traumatic brain injury through basic and clinical science research in order to develop effective therapies to enhance functional recovery for victims of traumatic brain injury. The purpose of the UCLA Brain Injury Research Center (BIRC) is to maintain a comprehensive basic and clinical scientific program in the field of TBI emphasizing translational research to develop effective therapies for head injured patients. To this end, the UCLA BIRC adheres to the research goal of applying knowledge obtained from basic science studies toward understanding the neurobiology of human TBI. Consequently, a fundamental commitment of the UCLA BIRC is to support technological advances in imaging, neurophysiology, molecular biology, modeling and behavioral neuroscience, which can be applied with equal rigor to experimental animal subjects as well as TBI patients. As such, UCLA maintains a center of excellence where students and faculty can come to receive training in this important endeavor. The technological capability of directly measuring genetic, neurochemical and neurophysiological processes associated with TBI provides a number of specific markers with which potential therapies can be evaluated. This capability of directly measuring the biology targeted by experimental therapies allows for not only evaluating specific scientific hypotheses, but also assures that recovery of function is linked to appropriate neurobiological processes. This concept is extremely important given that the results from repeated studies in the United States and Europe testing potential therapies have been very disappointing. Clearly, relying on traditional outcome measures without the ability to directly measure the proposed mechanisms responsible has limited our ability as a field to make a strong clinical impact to enhance recovery of function. Supporting the recently acquired technological advances in both imaging and in neurochemical measurements of the human brain, the UCLA BIRC is dedicated to relate outcomes to neurobiological substrates targeted for treatment. Consequently, a truly targeted approach to therapy will be developed. The UCLA BIRC has been the driving force behind a fundamental paradigm shift from limiting the understanding of basic mechanisms in animal studies to that of applying molecular imaging to translate basic experiments to the clinic. Having developed this innovative approach to the study of TBI, the BIRC has an obligation to accelerate its clinical and basic science efforts to explore other components of the pathobiology of TBI. Consequently, the allocation of funds from the State of California to the UCLA BIRC continues to provide the support necessary to establish and maintain a core center of excellence for the research of TBI across multiple campuses of the University of California. Recently, funds have been used to establish and maintain state-of-the-art-imaging capabilities for both experimental animals and human TBI patients. These imaging modalities incorporate positron emission tomography (PET), magnetic resonance imaging (MRI), MRI spectroscopy, cerebral microdialysis and computed tomography. Expansion of the basic science initiatives towards development, neuroplasticity and post-injury vulnerability have required advancement of existing programs in neurochemistry, neurophysiology, neurotransplantation, and molecular biology. All of these initiatives and the corresponding technological applications have been focused on the goal of enhancing functional recovery following TBI. As the primary goal of the UCLA BIRC is to effect the treatment of head injured patients, it is critically important that laboratories work in close association with clinical research teams. This allows experiments to be discussed and evaluated thereby fostering the translation of science into the clinical setting which is so vital to making appropriate progress in the field. Furthermore, the UCLA BIRC provides opportunities for training at both the graduate and postgraduate level in order that students acquire the technical and experience necessary for conducting both experimental and clinical research in the field of TBI. Trainees have joined the BIRC for periods of weeks to months from a variety of programs, including: The University of Texas, The University of Kentucky, Virginia Commonwealth University, Uppsala University, Nihon University, Milan University, University of Hannover, Cambridge, Brown, University of Pennsylvania The University of California, San Francisco, The University of California, Davis, The University of California, Irvine, The University of California, San Diego and The University of Pittsburgh. We will continue to accommodate highly motivated trainees whenever possible, tailoring their experiences as closely as their needs and our capabilities allow. Finally, resources of the UCLA BIRC state allocation continue to support the multi-campus University of California Neurotrauma Research Program. 1.3 The University Of California Neurotrauma Research Program A component of the UCLA BIRC state allocation continues to support a research initiative in TBI for the entire University of California system spanning all campuses. This program supports an annual University of California Neurotrauma Symposium, offers assistance for travel expenses for faculty and students wishing to present their research data related to TBI, and to provide supplemental support for individual research projects and workshops on TBI research. The fundamental mission behind this program is to support TBI injury research throughout all campuses of the University of California. Management, support and oversight of this program are the responsibility of the UCLA BIRC under the direction of Dr. David A. Hovda. The specific goals of the research funding are to: 1. Provide funding to encourage both basic and clinical science research into the topic of traumatic brain injury and recovery of function. 2. Develop and support a fellowship program where graduate and post-doctoral students and faculty can attend UCLA in order to receive research training in both clinical and basic scientific methodologies in the field of Neurotrauma. 3. Provide travel fellowships to the National and International Neurotrauma Society meetings. 4. Support an annual University of California Neurotrauma Symposium where research programs throughout the University of California can present their data, foster and discuss collaborations and address funding needs. The administrative structure of the University of California Neurotrauma Research Program includes the UCLA BIRC Executive Committee consisting of the senior leadership of the UCLA Brain Injury Research Center (see above). Funding and policy decisions are made by this committee in order to assure preservation of the BIRC mission and that an appropriate allocation of resources is maintained. The University of California Neurotrauma Advisory Board (see list below) advises the Executive Committee providing advice regarding the annual UC Neurotrauma Symposium, funding1 decisions, intra-campus clinical trials, developing of core facilities and grant development. This board meets on an annual basis in conjunction with the National Neurotrauma meeting and submits to Dr. Hovda minutes with its recommendations. In the spirit of shared governance, the Executive Committee continues to be responsive to the University of California Neurotrauma Advisory Board, assuring appropriate incorporation of all campuses into all of its initiatives. Dr. Hovda (or his representative) visits each campus annually in order to monitor scientific progress, program development and the fostering of young investigators into the field. Members of the University of California Neurotrauma Advisory Board: Dr. Linda Noble-Hauesslein, Professor of Neurosurgery, UC San Francisco Dr. Bruce Lyeth, Professor of Neurosurgery, UC Davis Dr. Paul Muizelaar, Professor and Chair, Neurosurgery, UC Davis Dr. Jeffrey Max, Professor, Psychiatry, UC San Diego In order to assure appropriate dissemination, the UCLA BIRC has developed and maintains a web site (www.birc.ucla.edu) highlighting the specific goals of the University of California Neurotrauma Program as well as providing announcements for upcoming meetings and funding opportunities. Along with the above methods of communication, the UCLA BIRC arranges for visiting lecture programs at each of the corresponding UC campuses thereby providing direct, personal contact to investigators.